Adult Acute Basophilic LeukemiaPhase 1NCT00383474

Tipifarnib and Bortezomib in Treating Patients With Acute Leukemia or Chronic Myelogenous Leukemia in Blast Phase

A Phase 1 study testing Bortezomib, Laboratory Biomarker Analysis and Tipifarnib in people with Adult Acute Basophilic Leukemia and Adult Acute Eosinophilic Leukemia, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This phase I trial is studying the side effects and best dose of tipifarnib and bortezomib in treating patients with acute leukemia or chronic myelogenous leukemia in blast phase. Tipifarnib and bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Adult Acute Basophilic Leukemia, Adult Acute Eosinophilic Leukemia, Adult Acute Megakaryoblastic Leukemia
What is being tested?: Bortezomib, Laboratory Biomarker Analysis and Tipifarnib
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 35 participants
Where: 1 siteUnited States
Study dates: Aug 2006to Jun 2012
Phase: Phase 1

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Meets 1 of the following disease-specific criteria:
Relapsed disease after =< 2 prior chemotherapy regimens (consolidation therapy excluded)
Primary-induction failure
Previously untreated and deemed unfit for or refusing cytotoxic chemotherapy
No hyperleukocytosis (leukemic blasts >= 30,000/mm^3)
No acute promyelocytic leukemia (M3)

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No active CNS leukemia
SGOT and SGPT =< 2 times upper limit of normal (ULN)
Bilirubin normal
Creatinine =< 1.5 times ULN
No uncontrolled hypertension, congestive heart failure, angina pectoris, or ventricular dysrhythmias
Not pregnant or nursing
Negative pregnancy test
No uncontrolled disseminated intravascular coagulation
Fertile patients must use effective contraception
Hormonal contraception must have been initiated ≥ 1 month prior to study entry
No active graft-vs-host disease
No active uncontrolled infection
No intrinsic impaired organ function
No known allergy to imidazole drugs
No neuropathy >= grade 1
No known hypersensitivity to bortezomib, tipifarnib, boron, or mannitol
No physical or psychiatric conditions that would preclude study participation, including poorly controlled psychosis
At least 48 hours since prior hydroxyurea
No prior tipifarnib, bortezomib, or investigational proteasomal inhibitors
No concurrent radiotherapy, chemotherapy, or immunotherapy
No concurrent enzyme-inducing antiepileptic medications (e.g., phenytoin, phenobarbital, or carbamazepine)
ECOG performance status 0-2
LVEF >= 40%
Pathologically confirmed diagnosis of 1 of the following:
Acute myeloid leukemia
Acute lymphoblastic leukemia
Chronic myelogenous leukemia in blast phase

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

Moffitt Cancer Center
Tampa, Florida, 33612

Other trials in United States

About this study

Official title: A Phase I Dose-Escalation Study of R115777 (Tipifarnib) Plus PS-341 (Bortezomib) in Relapsed or Refractory Acute Leukemias

Read the detailed description

PRIMARY OBJECTIVE:

Determine the dose-limiting toxicity and maximum tolerated dose of tipifarnib and bortezomib in patients with relapsed or refractory acute myeloid leukemia, acute lymphoblastic leukemia, or chronic myeloid leukemia in blast phase.

SECONDARY OBJECTIVES:

Determine the effect of this regimen on farnesyltransferase and proteasome inhibition in peripheral blood mononuclear cells in these patients.

II. Determine the clinical efficacy of this regimen in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11 and oral tipifarnib twice daily on days 1-14. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients with partial response or stable disease may continue therapy beyond 6 courses at the discretion of the investigator.

Cohorts of 3-6 patients receive escalating doses of bortezomib and tipifarnib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Blood is collected periodically for protein expression studies. Bone marrow aspirates obtained at baseline are examined by immunohistochemistry for Ki-67 activity.

Conditions: Adult Acute Basophilic Leukemia, Adult Acute Eosinophilic Leukemia, Adult Acute Megakaryoblastic Leukemia, Adult Acute Monoblastic Leukemia, Adult Acute Monocytic Leukemia, Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11
Being tested: Bortezomib, Laboratory Biomarker Analysis, Tipifarnib
Medical subject headings: Leukemia, Basophilic, Acute, Leukemia, Eosinophilic, Acute, Leukemia, Megakaryoblastic, Acute, Leukemia, Monocytic, Acute, Leukemia, Myelomonocytic, Acute, Leukemia, Myeloid, Acute, Leukemia, Erythroblastic, Acute, Blast Crisis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BortezomibDrug
Also called [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies
TipifarnibDrug
Also called R115777, Zarnestra
Given orally

Study groups in NCT00383474
Study group	Role	What they receive
Arm I	Experimental	Patients will receive an infusion of bortezomib twice a week for 2 weeks. They will also receive tipifarnib by mouth twice a day for 2 weeks. Receives: Drug: Bortezomib; Other: Laboratory Biomarker Analysis; Drug: Tipifarnib

What is being measured

The primary outcome is the main question the study is designed to answer.

Dose-limiting toxicity and maximum tolerated dose of tipifarnib and bortezomib
Measured: 21 days

Secondary outcomes (4)

Changes in apoptotic protein expression (Bim, Bax, AKT)
Measured: Baseline and day 8
Clinical efficacy (response rate) evaluated using the revised International Working Group Criteria (IWG) for AML
Measured: Up to 3 years
Farnesytransferase and proteasome inhibition in peripheral blood mononuclear cells
Measured: Day 8
Farnesytransferase and proteasome inhibition in peripheral blood mononuclear cells
Measured: Day 15

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 2006Jun 2012

First posted3 Oct 2006 (estimated)
Study startAug 2006
Primary completionJun 2012
Study completionJun 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Adult Acute Basophilic LeukemiaStudies of the same condition, open and under way.
More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 35 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00383474
Sponsor's protocol ID: NCI-2009-00147
Other IDs: NCI-2009-00147, CDR0000502258, MCC-14796, 7306, N01CM62208, P30CA076292
Status last verified: Apr 2013
First submitted: 29 Sep 2006
Last updated: 15 Apr 2015
Results posted: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Decitabine, Cytarabine, and Daunorubicin Hydrochloride in Treating Patients With Acute Myeloid Leukemia
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